6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

doi:10.1016/j.bmcl.2011.06.014

Bioorganic & Medicinal Chemistry Letters

Volume 21, Issue 16, 15 August 2011, Pages 4891-4899

https://doi.org/10.1016/j.bmcl.2011.06.014 Get rights and content

Abstract

A series of 6-aryl-3-pyrrolidinylpyridine analogs was explored as structurally novel negative allosteric modulators of the mGlu5 receptor lacking an alkyne or oxadiazole moiety. Compounds in this series were characterized by tractable SAR, good in vitro potencies and brain penetration in rodents.

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Acknowledgements

We are grateful to Drs. Mark Hayward, Qing-Ping Han, Chi Zhang and Xu Zhang, in the CPS Department, for determinations of physicochemical properties and the resolution of compound 11g, to Christina L. Bonvicino and Xiaosui Pu for in vitro pharmacology determinations and to Dr. Albert J. Robichaud for his support during this work and for helpful comments to this manuscript.

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6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Abstract

Graphical abstract

Section snippets

Acknowledgements

Neuropharmacology

Nat. Rev. Drug Discovery

Basic Clin. Pharmacol. Toxicol.

Pharmacol. Ther.

J. Pharmacol. Exp. Ther.

Neurogastroenterol. Motil.

J. Med. Chem.

Pharmacol. Rev.

G Protein-Coupled Receptors in Drug Discovery

Nat. Rev. Drug Discov.